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Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients

Background and aims: There is no established predictive marker for the treatment of renal cancer. Metastatic renal cell carcinoma (mRCC) patients are often treated with sunitinib, a tyrosine kinase inhibitor. Sunitinibs anti-cancer effect is at least partly mediated through interfering with angiogen...

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Autores principales: Niinivirta, Marjut, Enblad, Gunilla, Edqvist, Per-Henrik, Pontén, Fredrik, Dragomir, Anca, Ullenhag, Gustav J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705999/
https://www.ncbi.nlm.nih.gov/pubmed/29187872
http://dx.doi.org/10.7150/jca.20889
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author Niinivirta, Marjut
Enblad, Gunilla
Edqvist, Per-Henrik
Pontén, Fredrik
Dragomir, Anca
Ullenhag, Gustav J.
author_facet Niinivirta, Marjut
Enblad, Gunilla
Edqvist, Per-Henrik
Pontén, Fredrik
Dragomir, Anca
Ullenhag, Gustav J.
author_sort Niinivirta, Marjut
collection PubMed
description Background and aims: There is no established predictive marker for the treatment of renal cancer. Metastatic renal cell carcinoma (mRCC) patients are often treated with sunitinib, a tyrosine kinase inhibitor. Sunitinibs anti-cancer effect is at least partly mediated through interfering with angiogenesis. Our aim with the current study was to assess annexin A1 (ANXA1), which stimulates angiogenesis, as a predictive marker for sunitinib therapy in mRCC patients. Since previous studies have indicated a predictive potential for cubilin, we also investigated the predictivity of ANXA1 combined with cubilin. Methods: ANXA1 expression was analysed in tumor tissue from a cohort of patients with advanced RCC (n=139) using immunohistochemistry. Ninety-nine of the patients were treated with sunitinib in the first or second-line setting. Twenty-two of these were censored because of toxicity leading to the termination of treatment and the remaining (n=77) were selected for the present study. Results: Twenty-five (32%) out of seventy-seven of the tumors lacked ANXA1 in the cytoplasm. On statistical analyses using Kaplan-Meier method, aNXA1 negative tumors were significantly associated with a longer treatment benefit in terms of progression free survival (PFS). Overall survival was also significantly better for patients with ANXA1 negative tumors. The combined ANXA1 positive and cubilin negative expression could more accurately than ANXA1 alone define the group not benefitting from treatment. Conclusions: Our results indicate that cytoplasmic expression of ANXA1 is a negative predictive marker for sunitinib therapy in mRCC patients. A possible explanation for this finding is that sunitinibs anti-angiogenic effect cannot overcome the pro-angiogenic drive from many ANXA1 proteins.
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spelling pubmed-57059992017-11-29 Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients Niinivirta, Marjut Enblad, Gunilla Edqvist, Per-Henrik Pontén, Fredrik Dragomir, Anca Ullenhag, Gustav J. J Cancer Research Paper Background and aims: There is no established predictive marker for the treatment of renal cancer. Metastatic renal cell carcinoma (mRCC) patients are often treated with sunitinib, a tyrosine kinase inhibitor. Sunitinibs anti-cancer effect is at least partly mediated through interfering with angiogenesis. Our aim with the current study was to assess annexin A1 (ANXA1), which stimulates angiogenesis, as a predictive marker for sunitinib therapy in mRCC patients. Since previous studies have indicated a predictive potential for cubilin, we also investigated the predictivity of ANXA1 combined with cubilin. Methods: ANXA1 expression was analysed in tumor tissue from a cohort of patients with advanced RCC (n=139) using immunohistochemistry. Ninety-nine of the patients were treated with sunitinib in the first or second-line setting. Twenty-two of these were censored because of toxicity leading to the termination of treatment and the remaining (n=77) were selected for the present study. Results: Twenty-five (32%) out of seventy-seven of the tumors lacked ANXA1 in the cytoplasm. On statistical analyses using Kaplan-Meier method, aNXA1 negative tumors were significantly associated with a longer treatment benefit in terms of progression free survival (PFS). Overall survival was also significantly better for patients with ANXA1 negative tumors. The combined ANXA1 positive and cubilin negative expression could more accurately than ANXA1 alone define the group not benefitting from treatment. Conclusions: Our results indicate that cytoplasmic expression of ANXA1 is a negative predictive marker for sunitinib therapy in mRCC patients. A possible explanation for this finding is that sunitinibs anti-angiogenic effect cannot overcome the pro-angiogenic drive from many ANXA1 proteins. Ivyspring International Publisher 2017-10-23 /pmc/articles/PMC5705999/ /pubmed/29187872 http://dx.doi.org/10.7150/jca.20889 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Niinivirta, Marjut
Enblad, Gunilla
Edqvist, Per-Henrik
Pontén, Fredrik
Dragomir, Anca
Ullenhag, Gustav J.
Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients
title Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients
title_full Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients
title_fullStr Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients
title_full_unstemmed Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients
title_short Tumoral ANXA1 Is a Predictive Marker for Sunitinib Treatment of Renal Cancer Patients
title_sort tumoral anxa1 is a predictive marker for sunitinib treatment of renal cancer patients
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705999/
https://www.ncbi.nlm.nih.gov/pubmed/29187872
http://dx.doi.org/10.7150/jca.20889
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